RRC ID |
34752
|
著者 |
Jiang HC, Hsu JM, Yen CP, Chao CC, Chen RH, Pan CL.
|
タイトル |
Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons.
|
ジャーナル |
Proc Natl Acad Sci U S A
|
Abstract |
Decline in mitochondrial morphology and function is a hallmark of neuronal aging. Here we report that progressive mitochondrial fragmentation is a common manifestation of aging Caenorhabditis elegans neurons and body wall muscles. We show that sensory-evoked activity was essential for maintaining neuronal mitochondrial morphology, and this activity-dependent mechanism required the Degenerin/ENaC sodium channel MEC-4, the L-type voltage-gated calcium channel EGL-19, and the Ca/calmodulin-dependent kinase II (CaMKII) UNC-43. Importantly, UNC-43 phosphorylated and inhibited the dynamin-related protein (DRP)-1, which was responsible for excessive mitochondrial fragmentation in neurons that lacked sensory-evoked activity. Moreover, enhanced activity in the aged neurons ameliorated mitochondrial fragmentation. These findings provide a detailed description of mitochondrial behavior in aging neurons and identify activity-dependent DRP-1 phosphorylation by CaMKII as a key mechanism in neuronal mitochondrial maintenance.
|
巻・号 |
112(28)
|
ページ |
8768-73
|
公開日 |
2015-7-14
|
DOI |
10.1073/pnas.1501831112
|
PII |
1501831112
|
PMID |
26124107
|
PMC |
PMC4507213
|
MeSH |
Aging
Animals
Caenorhabditis elegans / enzymology
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins / physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
Longevity
Mitochondria / physiology*
Neurons / enzymology
Neurons / physiology*
Oxidation-Reduction
|
IF |
9.412
|
引用数 |
20
|
WOS 分野
|
MULTIDISCIPLINARY SCIENCES
|
リソース情報 |
線虫 |
fzo-1(tm1133)
drp-1(tm1108) |